History of human use of psychedelics

In the past, psychedelics like psilocybin, mescaline and ayahuasca have been used by different cultures around the world in ceremonial, spiritual and ‘healing’ rituals. Some continue to be used legally by the descendants of those indigenous cultures. Such rituals come with a rich and important history that inform about their role and use.

History of psychedelics in psychiatry

Prior to 1970 the classical psychedelics psilocybin, mescaline and d-lysergic acid diethylamide (LSD) were used in psychiatry as part of an ongoing process of psychotherapy for resistant forms of depression, anxiety and addictions. Research at that time, which was suboptimal by modern standards, suggested that they were helpful for some people when given within a medically controlled and psychologically supportive context.

After 1970, LSD, psilocybin and mescaline were legally designated ‘Schedule 1’ substances, meaning that they could not be prescribed by medical doctors outside of authorised research. Funding for research dried up in the wake of hardening socio-political attitudes towards psychoactive drugs in general. Consequently, this area of clinical research stopped without a clear view about whether psychedelic therapy was safe and effective.

Since 2000, there has been a slow but steady resurgence of clinical research interest into psychedelics and related compounds such as MDMA and ketamine. A growing number of clinical trials have been published. Here at KCL, we are part of this research.

The need for new paradigms of treatment in psychiatry

Whilst many patients with mental health problems get better with available treatments, a subgroup of people do not even though they try many different forms of treatment. This is sometimes called ‘treatment resistance’. This can lead to a variety of other problems that seriously impact on patients and the people around them. Treatment options are often limited and come with troublesome side effects or stigma. Therefore, new paradigms of treatment are needed and clinical research of new treatments is important. Psychedelic therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials.

Oversight of our trials

All of our clinical trials are authorised by the National Research Ethics Committee, who are a group of professionals and members of the public whose job is to scrutinise and ensure the rights and wellbeing of participants in clinical trials. All of our clinical trials are registered with the Medicine’s and Healthcare Products Regulatory Agency, who are a government funded body whose job is to ensure that treatment development and research is being conducted according to internationally agreed standards with interventions manufactured to proper standards. All of our trials are regularly reviewed by the Sponsors and the Ethics Committees, who are able to halt a trial if they think it is no longer appropriate for it to continue.

Completed Trials

The effects of psilocybin on cognitive function in healthy participants

In partnership with COMPASS Pathways researchers from King’s College London have established that psilocybin can be safely administered at doses of either 10mg or 25mg to up to six participants simultaneously.

The trial is now finished and results were published in The Journal of Psychopharmacology in March 2022. They represent an essential first step in demonstrating the safety and feasibility of psilocybin for use within controlled settings alongside talking therapy as a potential treatment for a range of mental health conditions.

Status	Completed, not recruiting
Participants	Adults
Clinical area	Healthy participants
Intervention	Psilocybin
Recruitment period	2018-2020
Funder	Compass Pathways
Sponsor	Compass Pathways

 

The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD) Study

King’s College London were part of a multi-centre trial led by COMPASS Pathways that is called P-TRD. The trial was conducted across 22 sites in 10 countries from Europe and the US. Adults with treatment resistant depression were given psilocybin at a dose of 25 mg, 10 mg, or 1 mg. The drug was administered together with psychological support and researchers measured changes in depression symptoms.

Status	Completed, not recruiting
Participants	Adults
Clinical area	Treatment resistant depression
Intervention	Psilocybin therapy
Recruitment period	2020-2021
Funder	Compass Pathways
Sponsor	Compass Pathways

 

An Exploratory Open-Label, Phase 1b, Ascending Dose Study to Evaluate the Effects of Oral 3 [2 (dimethylamino)ethyl]-1h-indol-4-yl Dihydrogen Phosphate (Psilocybin, BPL PSILO) on Cognition in Patients with Chronic Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)

Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA) are debilitating and there are few treatment options. With  funding from Beckley PsyTech researchers from King’s investigated  the efficacy of psilocybin at three doses for treating these headache attacks, particularly looking at its impact on thought processes.

Status	Completed, not recruiting
Participants	Adults
Clinical area	SUNHA
Intervention	3 doses of psilocybin
Recruitment period	2022
Funder	Beckley PsyTech
Sponsor	Beckley PsyTech

 

A Double-Blind, Randomized, Phase 1, First-in-Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of Intranasal 5 Methoxy N,N-dimethyltryptamine (5-MeO-DMT) in Healthy Subjects

In partnership with Beckley PsyTech, King’s researchers evaluated the safety and tolerability of the psychedelic 5 Methoxy N,N-dimethyltryptamine (5-MeO-DMT) which is found in a variety of plant species and secreted by one species of toad. It was administered nasally to healthy participants at one dosage and researchers assessed the percentage of participants that experienced any unfavourable and unintended signs, alongside various measures to assess what is happening to the drug when it is taken.

Status	Completed, not recruiting
Participants	Adults
Clinical area	Healthy participants
Intervention	5-Methoxy-N,N-Dimethyltryptamine
Recruitment period	2021 – 2022
Funder	Beckley PsyTech
Sponsor	Beckley PsyTech

  

Publications:

https://journals.sagepub.com/doi/full/10.1177/02698811211064720

 

An Open-Label, Phase 2, Multicenter Feasibility Study of Manualized MDMA- Assisted Psychotherapy with an Optional fMRI Sub-Study Assessing Changes in Brain Activity in Subjects with Posttraumatic Stress Disorder

With support from the Multidisciplinary Association of Psychedelic Studies (MAPS) we trialled MDMA therapy for PTSD for veterans. 

Status	Completed, not recruiting
Participants	Adults
Clinical area	PTSD
Intervention	MDMA
Recruitment period	2022 – 2023
Funder	MAPS
Sponsor	MAPS

 

The Safety and Tolerability of COMP360 in Participants with Post-traumatic Stress Disorder

With support from Compass Pathways, we explored the safety and tolerability of of COMP360 (psilocybin) given alongside psychological support to participants suffering from post-traumatic stress disorder. This trial was undertaken alongside colleagues in the United States.

Status	Completed, not recruiting
Participants	Adults
Clinical area	PTSD
Intervention	Psilocybin
Recruitment period	2022 – 2023
Funder	Compass Pathways
Sponsor	Compass Pathways

 

An Open-Label, Phase 2a Single Dose Study of 5-MeO-DMT in Patients With Alcohol Use Disorder

With the support of Beckley PsyTech we trialled 5-MeO-DMT given with structured psychological support for alcohol use disorder. 5-MeO-DMT is a short-acting psychedelic drug, which means that it induces an altered state of consciousness that can be characterised by mystical experiences, strong emotions, visions and distorted perceptions.

Status	Completed, not recruiting
Participants	Adults
Clinical area	Alcohol use disorder
Intervention	5-MeO-DMT with Structured Psychological Support
Recruitment period	2023-24
Contact	AUD-5MEODMT@kcl.ac.uk
Funder	Beckley PsyTech
Sponsor	Beckley PsyTech

 

With support from Transcend Therapeutics, we explored the safety and efficacy of methylone treatment in patients suffering from post-traumatic stress disorder.

Status	Completed, not recruiting
Participants	Adults
Clinical area	Post-traumatic stress disorder
Intervention	Methylone therapy
Recruitment period	2024
Contact	methylone@kcl.ac.uk
Funder	Transcend Therapeutics
Sponsor	Transcend Therapeutics